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      Impact of sex, fat distribution and initial body weight on oxytocin’s body weight regulation

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          Abstract

          Obesity is considered as a worldwide problem in both males and females. Although many studies have demonstrated the efficiency of oxytocin (Oxt) as an anti-obesity peptide, there is no comparative study of its effect in males and females. This study aims to determine factors (sex, initial body weight, and fat distribution) that may affect the ability of Oxt to regulate body weight (BW). With regard to sex, Oxt reduced BW similarly in males and females under both high fat diet (HFD) and standard chow-fed condition. The BW reduction induced by Oxt correlated with initial BW in male and female mice under HFD conditions. Oxt showed an equal efficacy in fat degradation in both the visceral and subcutaneous fat mass in both males and females fed with HFD. The effect of Oxt on BW reduction was attenuated in standard chow-fed male and female mice. Therefore, our results suggest that administration of Oxt is more effective in reducing BW in subjects with a high initial BW with increased fat accumulation. The present data contains important information for the possible clinical application of Oxt for the treatment of obesity.

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          Most cited references38

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          Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013.

          In 2010, overweight and obesity were estimated to cause 3·4 million deaths, 3·9% of years of life lost, and 3·8% of disability-adjusted life-years (DALYs) worldwide. The rise in obesity has led to widespread calls for regular monitoring of changes in overweight and obesity prevalence in all populations. Comparable, up-to-date information about levels and trends is essential to quantify population health effects and to prompt decision makers to prioritise action. We estimate the global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013. We systematically identified surveys, reports, and published studies (n=1769) that included data for height and weight, both through physical measurements and self-reports. We used mixed effects linear regression to correct for bias in self-reports. We obtained data for prevalence of obesity and overweight by age, sex, country, and year (n=19,244) with a spatiotemporal Gaussian process regression model to estimate prevalence with 95% uncertainty intervals (UIs). Worldwide, the proportion of adults with a body-mass index (BMI) of 25 kg/m(2) or greater increased between 1980 and 2013 from 28·8% (95% UI 28·4-29·3) to 36·9% (36·3-37·4) in men, and from 29·8% (29·3-30·2) to 38·0% (37·5-38·5) in women. Prevalence has increased substantially in children and adolescents in developed countries; 23·8% (22·9-24·7) of boys and 22·6% (21·7-23·6) of girls were overweight or obese in 2013. The prevalence of overweight and obesity has also increased in children and adolescents in developing countries, from 8·1% (7·7-8·6) to 12·9% (12·3-13·5) in 2013 for boys and from 8·4% (8·1-8·8) to 13·4% (13·0-13·9) in girls. In adults, estimated prevalence of obesity exceeded 50% in men in Tonga and in women in Kuwait, Kiribati, Federated States of Micronesia, Libya, Qatar, Tonga, and Samoa. Since 2006, the increase in adult obesity in developed countries has slowed down. Because of the established health risks and substantial increases in prevalence, obesity has become a major global health challenge. Not only is obesity increasing, but no national success stories have been reported in the past 33 years. Urgent global action and leadership is needed to help countries to more effectively intervene. Bill & Melinda Gates Foundation. Copyright © 2014 Elsevier Ltd. All rights reserved.
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            CD38 is critical for social behaviour by regulating oxytocin secretion.

            CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, catalyses the formation of Ca2+ signalling molecules, but its role in the neuroendocrine system is unknown. Here we show that adult CD38 knockout (CD38-/-) female and male mice show marked defects in maternal nurturing and social behaviour, respectively, with higher locomotor activity. Consistently, the plasma level of oxytocin (OT), but not vasopressin, was strongly decreased in CD38-/- mice. Replacement of OT by subcutaneous injection or lentiviral-vector-mediated delivery of human CD38 in the hypothalamus rescued social memory and maternal care in CD38-/- mice. Depolarization-induced OT secretion and Ca2+ elevation in oxytocinergic neurohypophysial axon terminals were disrupted in CD38-/- mice; this was mimicked by CD38 metabolite antagonists in CD38+/+ mice. These results reveal that CD38 has a key role in neuropeptide release, thereby critically regulating maternal and social behaviours, and may be an element in neurodevelopmental disorders.
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              The molecular biology of chronic wounds and delayed healing in diabetes.

              Wound healing is a complicated and integrated process. Although there is some tolerance in terms of redundancy and interrelated control mechanisms, pushing beyond such limits may contribute to delayed wound healing, and in extreme cases lead to chronic wounds/ulcers and thus potentially to lower extremity amputation. Diabetes is associated with such disruption in wound healing. Research in humans and in animal models has identified a large number of changes associated with diabetes at the molecular level in delayed wound healing and to a lesser extent in chronic diabetic ulcers. Better overall understanding of these changes and how they are interrelated would allow for specifically targeted treatment, thus ensuring improved quality of life for patients and providing savings to the high costs that are associated with all aspects of chronic diabetic ulcers. This review examines the work done at the molecular level on chronic diabetic ulcers, as well as considering changes seen in diabetes in general, both in humans and animal models, that may in turn contribute to ulcer formation.
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                Author and article information

                Contributors
                maejimay@fmu.ac.jp
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                17 August 2017
                17 August 2017
                2017
                : 7
                : 8599
                Affiliations
                [1 ]ISNI 0000 0001 1017 9540, GRID grid.411582.b, , Department of Pharmacology, Fukushima Medical University School of Medicine, ; Fukushima-shi, 960-1295 Japan
                [2 ]ISNI 0000 0001 0722 4435, GRID grid.267687.a, , Department of Animal Science, Faculty of Agriculture, Utsunomiya University, ; Utsunomiya-Shi, 321-8505 Japan
                [3 ]ISNI 0000 0001 0702 8004, GRID grid.255137.7, , Department of Endocrinology and Metabolism, Dokkyo Medical University, ; Mibu-Machi, 321-0293 Japan
                [4 ]Takasu Clinic, Nagoya-shi, 450-6208 Aichi Japan
                [5 ]ISNI 0000 0001 1017 9540, GRID grid.411582.b, , Advanced Clinical Research Center, Fukushima Global Medical Science Center, Fukushima Medical University, ; Fukushima-shi, 960-1295 Japan
                Article
                9318
                10.1038/s41598-017-09318-7
                5561196
                28819236
                d784bb2b-f463-4a9d-b5df-d1f3c584b1a2
                © The Author(s) 2017

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 15 December 2016
                : 26 July 2017
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